Identifying which patients will benefit most from immune checkpoint blockade (ICB) is an important clinical challenge. A study now finds that Vδ1⁺ γδ T cells are associated with better response to ICB in melanoma tumors with a lower neoantigen load and shows that some effector functions of PD-1⁺ Vδ1⁺ T cells are repressed after engagement of PD-1 by PD-L1.

Immune checkpoint blockade (ICB) therapies offer hope to patients with certain types of advanced-stage cancers, and understanding who is more likely to find meaningful benefit from these treatments is of utmost clinical relevance. In a study by Davies et al. in this issue of Nature Cancer, a specific subset of unconventional γδ T cell antigen receptor (TCR)-bearing T cells, Vδ1⁺ cells, were found to correlate with improved responses to ICB¹. Provocatively, this was found to be particularly true in tumors with a relatively low neoantigen burden¹, which poses a paradigm for further work on the emerging question of the role of γδ T cells in responses to ICB.